Clinical Features

Mechanisms of Adverse Reactions to RCM
Acute
Anaphylactoid		Likely related to osmolarity, which is known to augment basophil and mast cell histamine release. Complement activation may account for some reactions. Occur in 1-3% of patients who receive ionic RCM (0.22% of these reactions are severe life-threatening) and <0.5% of patients who receive nonionic (0.04% severe life-threatening)
IgE-mediated		Much less common than anaphylactoid reactions May play a role in severe reactions to non-ionic contrast media
Delayed
?Cell-mediated		Defined as reactions occurring 1 hour to 1 week after RCM, occur in approximately 1-3% of patients. Most are mild, self-limited cutaneous eruptions (often maculopapular) that may be T-cell mediated, although more serious reactions, such as SJS, TEN, and DRESS have been described.
Chemotoxic		Related to the chemical properties of the contrast agent, and they are dose and concentration dependent. They tend to occur in medically unstable patients who are debilitated. For example cardiotoxicity, neurotoxicity, and nephrotoxicity

Risk Factors

Risk factors for anaphylactoid reaction onset/severity to RCM include:

Female sex
Asthma
Atopy
History of previous reactions to RCM
Beta-blocker and/or the presence of cardiovascular conditions
Seafood allergy and/or iodine sensitivity is NOT a risk factor
- This includes patients with a history of contact dermatitis to iodine-containing solutions (e.g. povidone iodine)

For readministration of RCM to prior anaphylactoid reactors, premedication with corticosteroid and antihstamines significantly reduces (5-10 fold), but does not eliminate, the risk of anaphylactoid reaction

Time before procedure (hours))	Drug	Dose------------------------	Note
-13	Prednisone	1 mg/Kg PO Up to 50 mg	May substitute hydrocortisone 200 mg IV if unable to take PO
-7	Prednisone	1 mg/Kg PO Up to 50 mg	May substitute hydrocortisone 200 mg IV if unable to take PO
-1	Prednisone	1 mg/Kg PO Up to 50 mg	May substitute hydrocortisone 200 mg IV if unable to take PO
-1	Diphenhydramine---	1 mg/Kg PO/IM Up to 50 mg
-1 (optional)	Ranitidine	1-2 mg/Kg PO/IM Up to 150 mg--------	H2 receptor antagonists are beneficial in the treatment of anaphylaxis When the addition of H2 receptor antagonists 1 hour before RCM was studied, a modest increase in reaction rate was observed
-1 (optional)	Albuterol or Ephedrine-_-	4 mg or 25 mg PO	These agents may not be favorable from a risk-benefit standpoint in patients with cardiovascular disease

Alternative premedication protocol (Lieberman): Prednisone 50 mg PO at -12 hours, -6 hours, and -30 minutes prior to the RCM + diphenhydramine 50 mg PO -30 minutes prior to RCM
Alternative protocol (ACR): methylprednisolone 32 mg PO at -12 hours and -2 hours prior to RCM +/- Diphenhydramine 50 mg PO -1 hour prior to RCM
For anaphylactoid reactions despite premedication, consider graded challenge or desensitization
- Lieberman: Administer serial dilutions of RCM in saline, beginning with a 1:1000 dilution at an initial dose of 0.2 mL. Double the dose every 10 minutes, progressing through the 1:100, 1:10, and finally, the full strength preparation. Ten minutes after you have administered 1 mL of the full strength, you could proceed with the desired dose of radiocontrast.
- Gandhi:

In decreasing order of desirability:

Methylprednisolone 40 mg or hydrocortisone 200 mg IV q4h until RCM + diphenhydramine 50 mg IV -1 hour prior to RCM
Dexamethasone 7.5 mg or betamethasone 6 mg IV q4h until RCM + diphenhydramine 50 mg IV -1 hour prior to RCM; recommended for patients with known allergy to methylprednisolone, aspirin or NSAIDs, especially if asthmatic
Diphenhydramine 50 mg IV alone (e.g. if contrast study to be done in <4 hours)

IgE-mediated reactions	In IgE-mediated reactions, negative skin testing may predict which RCM agents can be given safely For example, SPT to undiluted agent followed by intradermal at 1000 and 10 fold dilutions has been reported, and readministration of agents causing positive skin tests is avoided
Delayed reactions	Delayed reading of intradermals (at 24 h) and patch testing (at 24, 48, 72 h) with contrast media has been reported Patients with delayed reactions to a RCM agent are likely to have positive delayed skin tests to other agents that are similar in chemical structure Negative delayed skin testing may predict which RCM agents can be given safely

Note

Reactions to RCM can occur when administered via nonvascular routes (e.g. during histosalpingograms, myelograms, intraarticular injections, and via other routes of administration). A patient receiving nonvascular RCM with a history of reaction to RCM should be treated using the same protocols outlined above.

Gadolinium (Gd) contrast agents are used to enhance MRI images, can be divided into 3 categories:
- Non-ionic linear (open-chain): Omniscan, Optimark
- Ionic linear (open-chain): Magnevist, MultiHance, Eovist, Ablavar
- Macrocyclic: ProHance, Dotarem, Gadovist